The hair follicle, which is grown from a lower part of the primitive epidermis and extends into a deeper skin layer, is a distinctive organ found in mammalian skin. A cell plug known as a follicle or dermal papilla cell exists in the base of the hair follicle (Stenn and Paus, Physiol. Rev., 81: 449 (2002)), and the papilla is essential in the normal circulation of the hair follicle (Oliver, Embryol. Exp. Morph. 15: 3311 (1966); and Oliver, Embryol. Exp. Morph. 16: 231 (1966)) and the growth of the hair shaft. The hair shaft is a thread-shaped structure formed of epithelial cells composed of keratin filaments and filament-aggregating proteins tightly attached thereto.
Human hairs fall out and again produce while cyclically repeating anagen, catagen, and telogen phases. The cycle of growth in the hair cycle is determined by regulation of hormones or other growth factors. Severe stress or malnutrition may advance the catagen and telogen phases, leading to severe hair loss (American Journal of Pathology, 162(3) (2003), (Arck, Petra Clara; Handjiski, Bori)).
In cases of male-pattern baldness, the hair follicles at the front and top of the scalp are sensitive to androgen. Thus, male-pattern baldness corresponds to the minimization of hair follicles rather than the destruction of hair follicles, and is caused by excessive secretion of the male hormone androgen. The excessive secretion of androgen results in the activation of 5-α reductase, converting testosterone into dihydrotestosterone (DHT). The resulting dihydrotestosterone shortens the cycle of hair growth and miniaturizes hair follicles, decreasing the number of thick strong adult hairs, leading to hair loss.
In general, hair loss increases with aging. For example, different disorders, such as cicatricial alopecia or scar conditions associated with burns or compression injury, may cause severe hair loss. Several substances as medicaments have been used to treat such a hair loss phenomenon, but the medicaments are expensive or cause several adverse effects.
In addition, these medicaments have drawbacks in that the sustained use thereof is required; hair loss again occurs when the use thereof is stopped; there are individual differences in efficacy; and side effects vary from person to person.
Furthermore, raw materials used as cosmetics have an advantage of being inexpensive, but their efficacy is not great since they contain ingredients derived from plant extracts. Therefore, there is an increasing need in the art for novel effective ingredients that are more economical in terms of costs.
Two available drugs known so far (minoxidil and finasteride) might delay additional hair loss, but do not induce the regeneration of new hair follicles. Among hair cosmetics, a lot of anti-hair loss products using plant extracts and the like have also been released.
For example, the products using plant extracts and the like that have been developed include: products containing extracts of sophora root, chili pepper, swertia, morus bark, morus leaves, ginseng, licorice, peony, foxglove, fennel, cornus fruit, garlic, and the like; products wherein a composition containing xanthines and growth hormones is added to improve cellular metabolism suppressed by excessive dihydrotestosterone and stimulate hair growth induced by growth hormones, thereby preventing hair loss and attaining hair production, leading to a hair growth stimulating effect; hair production stimulating products that supply nutrients to the scalp and hair through the development of products containing minerals, vitamins, and extracts of green tea, rosemary, mugwort, or licorice, in order to stimulate hair production and hair growth, and have effects in the prevention of hair loss and the stimulation of hair growth; and products for male-pattern baldness wherein the substances, such as vitamin B, vitamin C, vitamin D, vitamin E, nicotinic acid, pantothenic acid, biotin, and folic acid, are mixed with plant extracts to inhibit 5-α reductase, thereby preventing the production of dihydrotestosterone in the metabolism of male hormones and helping hair metabolism. However, products that affect even the production of new hair are difficult to find.
Skin cells produce melanin in melanosomes of melanocytes that are present in the basal epidermal layer, as a defense mechanism for the stimulation of ultraviolet light, environmental pollution, and other external factors. Melanin is an important factor to determine the color of skin, eyes, and hair of animals. Hypomelanosis is also known as a risk factor of skin cancer.
Asians are sensitive to the overproduction of melanin, and thus many whitening-related studies for melanogenesis inhibition have been conducted. In recent years, the demand against vitiligo, which is caused by melanogenesis inhibition, is also increasing, and thus studies therefor are being conducted.
Vitiligo is an acquired decolorizing disease wherein milky spots of several sizes and shapes are shown due to apoptosis or necrosis of melanocytes.
Vitiligo is a relatively common disease that occurs in about 1% of the population around the world, and there is no difference in the disease by race or area. Regarding the occurrence ages, vitiligo occurs most frequently at ages of 10 to 30 years, with 95% occurring before the age of 40, and 30% of the patients have a family history.
The causes of vitiligo have not yet been accurately revealed, but there are various theories, such as autoimmune hypothesis, neural hypothesis, and melanocyte self-destruct hypothesis. The autoimmune hypothesis is that the destruction or dysfunction of melanocytes is caused by the expression of auto-antibodies to melanocytes-based antigens, or melanocytes are destroyed by lymphokines secreted by cytotoxic lymphocytes or activated lymphocytes. The neural hypothesis is that hydrogen peroxide associated with stress is generated due to abnormal catecholamine biosynthesis and increased monoamine oxidase, resulting in the destruction of melanocytes, and vitiligo may occur along the ganglion or vitiligo may occur after nerve damage or stress. The melanocytes self-destruct hypothesis is that intermediate metabolites or phenol complexes as final metabolite of the melanogenic process are accumulated in melanocytes, resulting in cell destruction. Besides, various factors, such as inherent cellular defects, genetic factors, apoptosis, calcium metabolic disorders, are suggested.
Melanin is synthesized from melanocytes, and plays an important role in skin protection by the irradiation of UV light or the absorption of toxic substances and chemical substances. Therefore, people having no occurrence of normal melanin synthesis have an appearance problem in that the skin becomes white in part rather than whole, causing spots, and have a severe problem of being sensitive to external stimulations.
Tyrosinase, tyrosinase related protein-1 (TRP-1), and tyrosinase related protein-2 (TRP-2), which are important enzymes in melanin synthesis, act as catalysts for oxidative reactions (Pigment Cell Res. 14 (6): 43744).
Here, tyrosinase acts to oxidize tyrosine into L-3,4-dihydroxyphenylalanine (DOPA) and DOPA into DOPA quinine, and TRP-1 is dihydroxyindole carboxylic acid oxidase and involved in the conversion of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indol-5,6-quinone-2-carboxylic acid.
TRP-1 also serves to stabilize tyrosinase and regulate activity thereof. TRP-2, which is the DOPA chrome tautomerase, converts DOPA chrome into DHICA to form eumelanon and pheomelanon, constituting melanocytes, and the ratio thereof determines the colors of skin, hair, eyes, and the like.
The melanin synthesis is activated by UV irradiation and -melanocyte stimulating hormone (MSH). Here, α-MSH, which is a peptide hormone, is known to be produced by ultraviolet light and made from several cells including those of the pituitary gland and skin.
Here, α-MSH acts on melanocortin receptors (MCR) of melanocytes by paracrine to regulate the activity of the transcription factor microphthalmia-associated transcription factor (MITF), thereby regulating the activity of tyrosinase, DHICA oxidase (TRP-1), DOPAchrometautomerase (TRP-2), and the like, which play important roles in melanin synthesis (THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 273, No. 31, Issue of July 31, pp. 195609565, 1998).
It has been reported that the stimulation of melanocytes by UV or α-MSH leads to the activation of tyrosinase by p38 or protein kinase A (PKA), respectively. In these two pathways, especially, the α-MSH->cAMP->PKA pathway plays an important role in melanin synthesis. The increase in cAMP stimulates the phosphorylation of cAMP-responsive element binding protein (CREB), increasing the expression of the transcription factor MITF, which enhances the activity of tyrosinase and increases the mRNA expression of tyrosinase (Nucleic Acids Res. 30 (14): 3096106, Pigment Cell Melanoma Res 21 (6): 66576).
Asian people including Koreans want to have light skin colors, and thus have conducted many studies about whitening components inhibiting melanogenesis. However, melanin is synthesized from melanocytes in the skin, and plays an important role in skin protection by the irradiation of UV or the absorption of toxic substances and chemical substances. Since the absence of normal synthesis of melanin makes the skin sensitive to external stimulation and shows abnormal external appearances, the treatment for normal melanin synthesis is needed and studies therefor have been also conducted. So far, the development of techniques for stimulating melanin synthesis has not been sufficiently conducted.